PFS is not a problem. By no means, affinitor can reach 12 months PFS with every trial indicated around 6 months. What's interesting is the peek of OS data. Will half year of extra PFS translate into meaningful OS. That's the biggest question for cabo's future plan.
I asked my crystal ball: IF everolimus' median PFS is 5 months and trigger had been reached on 4/1/2015, what do we expect from cabo? It tells me: 12.
disclaimer: my crystal simulation also assume: 1/1 to 4/1, random enrollment to 50% and started immediately to dose, 4/1 to 7/1, 50%.
It all depends how well the everolimus is doing over expectation. I tried 183 days for its median, and we are still very good against it. I don't think PFS is a problem.
Let's assume cabo has already been approved for 2nd line RCC, and it beats Sunitinib with statsig in PFS and OS. And NCT01835158 is a head to head compare with existing 1st line drug with 150 patients. Is it enough for EXEL to ask FDA to move cabo up to 1st line?
The 5 v 7.5 assumption is broken. Smashed! The focus is on how afinitor is behaving comparing to expectation.
If it's still 5, our PFS is getting closer to expected OS.
If a company is a prey of big companies, its price can be kept very low. The big one will snap it at low price. The two companies I owned with very very successful products were stolen were: MEDX and MITI.
Any chance just give us PFS readout, and then continue with other analyses like safety, OS, pharmacokinetics, etc.
That's possible since PFS itself is the very criterion for cutting-off. The second that portion of patients is unblinded, PFS is over there.
Let me revisit my crystal ball. Let's assume cut off date to be 7/1/2015. If we want cabo branch to be 15mos, since cabo branch contributes 50%/2, the afi branch should contribute 90%/2. Afinitor's PFS should be less than 5mos. The reading from history, aff's PFE were 4.8-6. To be safe and fair, I always give it 6mos. My conclusion is 13-14, a little more than double or half year ahead. I don't worry about PFS, or approval. Just eager to see if half year's PFS increase can translate into some OS benefits. A peek into this not-matured analysis may give us some hints.
I don't have my simulation crystal ball at hand now since I am not at home. But still can do a rough estimate. Assume everolimus has 7 months, on 07/01 this branch may have about 77% PFS events. For a total 69% events, cabo should have 61% events. For a 15 months estimate time, my gut feeling is about 11 months. 11 vs 7, not too much to worry about.
If 15 months and 20 months medians hold true, my voodoo crystal ball told me, more than 40% of first 375 patients have encountered OS events. It's sad, and I didn't believe my crystal ball told me so. With these numbers, OS data in the interim(or, whatever you call it) analysis might not be matured(btw, crystal ball also told me we will have final analysis on next Feb or around), but surely will give us some ideas.
That's way too optimistic. My crystal ball told me: if 6 vs 14, on 5/15/2015, events will be more than 70%, greater than preset 69%. or 5.5 v 15. If cutoff date is after June, pfs will be greater than everolimus' OS. If everolimus performs exactly as anticipated, trial will be called off by then.
“How many PFS events of the first group has happened till now?" This is a question everyone wants an answer but the analysts may not ask.
Or the answer is "This trial is ongoing, but we cannot disclose the numbers. We will let everybody know ASAP after the analysis done."
Not necessarily. If 5 vs 11, on 4/11/2015, we've already passed the 69% mark. Even 6 vs 11, we've reached that mark. So long as afinitor doesn't outperform expectation way too much, we are in very good shape.
7 months for everolimus? Not a big deal. Even everolimus has 7 months PFS, cabo still much longer than #$%$ very simple: if both are 7, we've already reached 69%.
That's why I think a peek into OS is important. The future of cabo and exel depends more and more on trials with OS as primary endpoint. We cannot afford to go after only PFS.
As we are entering second quarter of 2015, everybody panic. Unless the company tells you how many events of the first 375 patients have happened, we will remain so indefinitely.